A Study to Assess the Safety and Tolerability of Nusinersen (ISIS 396443) in Participants With Spinal Muscular Atrophy (SMA).

NCT ID: NCT02462759

Last Updated: 2021-02-17

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 21 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-08-19
• Study Completion Date: 2018-09-24

Brief Summary

The primary objective of Part 1 of this study is to assess the safety and tolerability of Nusinersen in participants with SMA who are not eligible to participate in the clinical studies ISIS 396443-CS3B (NCT02193074) or ISIS 396443-CS4 (NCT02292537). The secondary objective of Part 1 of this study is to examine the pharmacokinetics (PK) of Nusinersen in participants with SMA. The primary objective of Part 2 of this study is to assess the long-term safety and tolerability of Nusinersen in participants with SMA who participated in Part 1 and completed their End of Part 1 Evaluation assessments. The secondary objective of Part 2 of this study is to examine the PK of Nusinersen in participants with SMA who participated in Part 1 and completed their End of Part 1 Evaluation assessments.

Detailed Description

Part 2 is an Open Label extension phase.

Conditions

Spinal Muscular Atrophy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Nusinersen

Administered by intrathecal injection.

Group Type: EXPERIMENTAL

Nusinersen

Intervention Type: DRUG

Administered by intrathecal injection.

Sham Procedure

Small needle prick on the lower back at the location where the IT injection is normally made.

Group Type: SHAM_COMPARATOR

Sham Procedure

Intervention Type: PROCEDURE

Small needle prick on the lower back at the location where the IT injection is normally made.

Interventions

Nusinersen

Administered by intrathecal injection.

Intervention Type: DRUG

Sham Procedure

Small needle prick on the lower back at the location where the IT injection is normally made.

Intervention Type: PROCEDURE

Other Intervention Names

BIIB058; ISIS SMNRx; ISIS 396443; Spinraza

Eligibility Criteria

Inclusion Criteria

• Genetic documentation of 5q SMA homozygous gene deletion, mutation, or compound heterozygote.
• Onset of clinical signs and symptoms consistent with SMA at ≤6 months of age and have documentation of 3 SMN2 copies OR onset of clinical signs and symptoms consistent with SMA at ≤6 months of age, >7 months of age (211 days) at screening, and have documentation of 2 SMN2 copies OR onset of clinical signs and symptoms consistent with SMA at >6 months of age, are ≤18 months of age at screening, and have documentation of 2 or 3 SMN2 copies.
• Meets age-appropriate institutional criteria for use of anesthesia/sedation, if use is planned for study procedures.
• Medical care, such as routine immunizations meets and is expected to continue to meet guidelines set out in the Consensus Statement for Standard of Care in SMA, in the opinion of the Investigator.
• Participants with 2 SMN2 copies must reside within approximately 9 hours' ground-travel distance from a participating study site for the duration of the study.

Exclusion Criteria

• Meets additional study related criteria.
• Any previous exposure to ISIS 396443; previous dosing in this study or previous studies with ISIS 396443.
• Signs or symptoms of SMA present at birth or within the first week after birth.
• Ventilation for ≥16 hours per day continuously for >21 days at screening.
• Permanent tracheostomy, implanted shunt for CSF drainage, or implanted central nervous system (CNS) catheter at screening.
• History of brain or spinal cord disease that would interfere with the LP procedure, CSF circulation, or safety assessments.
• Hospitalization for surgery (e.g., scoliosis surgery), pulmonary event, or nutritional support within 2 months prior to screening, or hospitalization for surgery planned during the study.
• Clinically significant abnormalities in hematology or clinical chemistry parameters or Electrocardiogram (ECG), as assessed by the Investigator.
• Treatment with an investigational drug for SMA (e.g., albuterol/salbutamol, riluzole, carnitine, sodium phenylbutyrate, valproate, hydroxyurea), biological agent, or device within 30 days prior to screening. Any history of gene therapy, prior antisense oligonucleotide (ASO) treatment, or cell transplantation.

For Part 2 only:

To be eligible to participate in Part 2 of this study, participants must meet the following eligibility criteria at the time of consent to participate in Part 2:

Participation in Part 1 and completion of the End of Part 1 Evaluation assessments.

Ability of parent(s) or legal guardian(s) to understand the purpose and risks of the study and to provide signed and dated informed consent on the Part 2 informed consent form (ICF) and authorization to use confidential health information in accordance with national and local participant privacy regulations.

Able to complete all study procedures, measurements, and visits, and parent or legal guardian/participant has adequately supportive psychosocial circumstances, in the opinion of the Investigator.

Participants will be excluded from the Part 2 if they meet the following exclusion criterion at the time of consent into Part 2 of the study:

Any significant change in clinical status, including laboratory tests that, in the opinion of the Investigator, would make them unsuitable to participate in Part 2. The Investigator must reassess the subject's medical fitness for participation and consider any diseases that would preclude treatment.

• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Biogen

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director

Role: STUDY_DIRECTOR

Biogen

Locations

David Geffen School of Medicine at UCLA

Los Angeles, California, United States

Connecticut Childrens Medical

Hartford, Connecticut, United States

The Johns Hopkins Hospital

Baltimore, Maryland, United States

Gillette Children's Specialty Healthcare

Saint Paul, Minnesota, United States

The University of Texas Southwestern Medical Center

Dallas, Texas, United States

Seattle Children's Research Institute

Seattle, Washington, United States

LMU-Campus Innenstadt

München, , Germany

Countries

United States; Germany

References

Acsadi G, Crawford TO, Muller-Felber W, Shieh PB, Richardson R, Natarajan N, Castro D, Ramirez-Schrempp D, Gambino G, Sun P, Farwell W. Safety and efficacy of nusinersen in spinal muscular atrophy: The EMBRACE study. Muscle Nerve. 2021 May;63(5):668-677. doi: 10.1002/mus.27187. Epub 2021 Feb 16.

Reference Type: DERIVED

PMID: 33501671 (View on PubMed)

Provided Documents

Document Type: Statistical Analysis Plan

View Document

Document Type: Study Protocol

View Document

Related Links

http://clinicalresearch.biogen.com/Content/Studies/232SM202%20Biogen.comPacket_Redacted.pdf

Clinical Study Report (CSR) Synopsis - a results summary

Other Identifiers

2014-003657-33

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

232SM202

Identifier Type: -

Identifier Source: org_study_id